It is well known that the myocardium can increase the strength of its contraction by increasing both the amount of calcium released to activate the myofilaments and the extent to which the myofilaments bind the calcium. Both of these changes can be regarded as increases in calcium activation. A major aim of the proposed experiments is to determine whether the myocardium can also enhance the contractile process independently of the effects on the calcium activating system. The applicant's preliminary studies in muscles containing a predominance of slow, V3, myosin indicate that the changes in contractility produced by beta adrenergic stimulation are not different than those produced by post extrasystolic potentiation, which is believed to increase only calcium activation. Experiments by others indicate that beta stimulation augments only the contraction of fast, V1, myosin, and the proposal has been made that this increase is specifically due to selective activation of the myosin, rather than a direct enhancement of contractile activity. The applicant's first experiments therefore would be to measure the effects of beta-adrenergic stimulation in muscles containing only V1 myosin to determine whether enhancement or increased activation occurs. In addition, the applicant would test the effects of alpha-adrenergic stimulation in both V1 and V3 muscles because of the report that this stimulation selectively activates the V3 isoform. The applicant would then study the effects of both alpha- and beta-stimulation on muscles having mixtures of myosin isoforms to determine whether selective activation of one isoform occurs. Once the effects of both types of adrenergic stimulation on intact muscle are known, the applicant would examine their effects in a "hyperpermeable", partially skinned preparation that can be activated by externally applied calcium and remains sensitive to adrenergic stimulants. This preparation would be used to separate the adrenergic effects on the calcium activating system from the direct effects on the contractile system.